Overcoming Immune Evasion in Staphylococcus aureus: Strategies for Rational Vaccine Design.

IF 3.8 2区医学 Q2 CHEMISTRY, MEDICINAL

ACS Infectious Diseases Pub Date : 2025-09-12 DOI:10.1021/acsinfecdis.5c00569

Khyber Shinwari, Brenda Vieira, Isabelle Ciaparin, Anders P Hakansson, Michelle Darrieux, Thiago Rojas Converso

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Abstract

Staphylococcus aureus remains one of the most elusive targets in bacterial vaccinology, primarily due to its complex immune evasion strategies and the phenomenon of immune imprinting. Despite decades of research and numerous clinical trials, no vaccine has demonstrated protective efficacy in humans. This review examines the underlying reasons for these failures and proposes a rational, integrative framework for next-generation vaccine development. Recent advances in reverse vaccinology, omics-driven antigen discovery, immunoinformatics, and artificial intelligence are highlighted as tools to identify conserved, immunogenic, and subdominant antigens. The review also discusses approaches for neutralizing virulence factors, disrupting biofilm-associated mechanisms, and circumventing dysfunctional immune memory. Particular emphasis is placed on the design of multivalent vaccine formulations capable of addressing the antigenic redundancy and immune modulation employed by S. aureus. By aligning systems biology with precision vaccinology, this review outlines a translational strategy to overcome the long-standing obstacles in the development of a safe and effective S. aureus vaccine.

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克服金黄色葡萄球菌的免疫逃避：合理的疫苗设计策略。

金黄色葡萄球菌仍然是细菌疫苗学中最难以捉摸的靶标之一，主要是由于其复杂的免疫逃避策略和免疫印迹现象。尽管经过数十年的研究和大量的临床试验，没有一种疫苗证明对人类有保护作用。这篇综述探讨了这些失败的潜在原因，并为下一代疫苗的开发提出了一个合理的综合框架。在反向疫苗学、组学驱动抗原发现、免疫信息学和人工智能方面的最新进展被强调为识别保守、免疫原性和亚显性抗原的工具。综述还讨论了中和毒力因子、破坏生物膜相关机制和规避功能失调免疫记忆的方法。特别强调的是设计多价疫苗配方，能够解决抗原冗余和金黄色葡萄球菌采用的免疫调节。通过将系统生物学与精确疫苗学相结合，本综述概述了一种转化策略，以克服开发安全有效的金黄色葡萄球菌疫苗的长期障碍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES

CiteScore

9.70

自引率

3.80%

发文量

213

期刊介绍： ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.